Utility of Serum Procalcitonin and Its Clearance in Predicting Outcomes in COVID-19 Patients.

Introduction Identification of coronavirus disease 2019 (COVID-19) patients at risk of worse clinical outcomes is crucial to improving patient care. Various biochemical markers have been used to predict outcomes in such patients. We aimed to evaluate the role of serum PCT (procalcitonin) and the utility of PCT clearance (PCTc) in predicting the outcome of patients with COVID-19 illness. Methods We prospectively included 39 patients with severe or critical COVID-19 illness with an age equal to more than 18 years. In addition to routine baseline investigations, serum PCT was measured at admission (PCT1) and day 5 of hospitalization (PCT2). PCTc was calculated using the formula [Formula: see text]. Results We observed that serum PCT at admission was significantly higher in non-survivors (median: 1.9 ng/ml IQR: 0.51-4.23) compared to survivors (median 0.35 (IQR: 0.1-1.2), p 0.002). On serial serum-PCT estimation, non-survivors had persistently elevated serum-PCT (median PCT1:1.9 ng/ml (IQR: 0.51-4.23) to median PCT2: 1.9ng/ml (IQR: 0.83-2.72), p 0.51) than survivors (median PCT1:0.35ng/ml (IQR: 0.1-1.19) to median PCT2: 0.15ng/ml (IQR: 0.05-0.29), p 0.01). However, no difference in serum PCTc was observed between the two groups (median: 35.3% (IQR: 12.5-84.9) in survivors vs. 71.7% (33.3-91.7) in non-survivors, p = 0.165). Conclusion Serum PCT is a potential biochemical marker that could predict outcomes in COVID-19 patients. Measurement of serial serum PCT and estimation of PCT clearance may serve as better predictors than a single value; however, well-designed studies are required to identify the definite role of serum PCT in COVID-19 patients of varying severity.

Addition of Mask to High-flow Nasal Oxygen: A Strategy to Improve Oxygenation in Hypoxemic Respiratory Failure Secondary to COVID-19.

PURPOSE: High-flow nasal cannula (HFNO) reduces the need for invasive mechanical ventilation in COVID-19 patients with hypoxemic-respiratory failure. During HFNO entrainment of room air dilutes the delivered fractional inspiratory oxygen (FiO2), thereby preventing improvement in oxygenation. The placement of a mask over HFNO to improve oxygenation has provided conflicting results. We aimed to determine and compare the effect of placing various mask types over HFNO on oxygen saturation (SPO2). MATERIALS AND METHODS: In this prospective physiological study 40 patients with COVID-19-associated hypoxemic respiratory failure on HFNO with O2 concentration <92% were included. The effect of placing different masks over HFNO on oxygenation, respiratory rate, heart rate, blood pressure, patient comfort, and partial pressure of carbon dioxide level (pCO2) was recorded after a prespecified time interval. RESULTS: We observed a significantly higher mean SPO2 and lower mean respiratory rate on using various study masks over HFNO compared to HFNO alone. On comparing various mask types, the use of N95 masks and nonrebreather (NRB) masks with O2 showed a significant increase in O2 concentration and reduction in respiratory rate compared to surgical mask (SM) and NRB without O2. The proportion of patients who achieved SPO2 of >92% was higher with the use of N95 masks (47.5%) or NRB with O2 (45%) over HFNO compared to SM (35%) and NRB without O2 (35%). No significant change was observed in heart rate, blood pressure, and CO2 level with the use of any mask over HFNO. CONCLUSION: This study demonstrates improvement in oxygenation and reduction in respiratory rate with the use of various masks over HFNO in patients of COVID-19-related hypoxemic-respiratory-failure. Significantly greater benefit was achieved with the use of N95 or NRB with O2 compared to SM or NRB without O2.

Association of IFN-gamma and IL-10 gene variants with the risk of extrapulmonary tuberculosis.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) is a chronic infectious disease. Interferon-gamma (IFN-γ) is an important cytokine imparting resistance to mycobacterial diseases. It is believed that IFN-γ and Interleukin-10 (IL-10) play divergent roles in the host immune system against MTB infection. IL-10 is an important inhibitory cytokine and helps balancing the inflammatory and immune responses. IL-10 is involved in down regulation of Th1 cytokines, MHC class II antigen and co-stimulatory molecular expression on macrophages, while IFN-γ results in macrophage activation allowing them to exert the microbicidal role. The objectives were to find out the association of IL-10 (-1082 A/G) and IFN-γ (+874 A/T) single nucleotide polymorphisms (SNPs) with extrapulmonary tuberculosis in ethnic Kashmiri population. A total of 100 extrapulmonary tuberculosis cases and 102 healthy controls were analyzed for IL-10 (-1082 A/G) and IFN- γ (+874 A/T) SNPs using Allele-Specific PCR. We found a significant association of IFN-γ + 874 'TT' genotype with extrapulmonary tuberculosis (p = 0.006) and in case of IL-10 (-1082 A/G) we found a significant association with extrapulmonary tuberculosis under recessive model (GG vs GA + AA) (p = 0.03) in Kashmiri population. IL-10 (-1082 A/G) and IFN-γ (+874 A/T) have a significant association with extrapulmonary tuberculosis in ethnic Kashmiri population.

Rickettsial Infections among the Undifferentiated Febrile Patients Attending a Tertiary Care Teaching Hospital of Northern India: A Longitudinal Study.

BACKGROUND: Acute undifferentiated febrile illness (AUFI) is one of the most daunting challenges a physician faces in such settings. Among AUFI, rickettsial infections are most common and related infections (such as anaplasmosis, ehrlichiosis, and Q fever) which are caused by an unusual type of bacteria that can live only inside the cells of another organism. The present study was therefore planned with an objective to estimate the prevalence of rickettsial infection among patients of undifferentiated fever and to determine any association of socio-demographic characteristics with rickettsial disease. MATERIALS AND METHODS: Patients presenting with febrile illness and admitted or attending out-patient department of Sher-i-Kashmir Institute of Medical Sciences, Srinagar was approached and recruited in the study. Weil Felix Assay, enzyme-linked immunosorbent assay and indirect immunofluorescence assay were done to detect the anti-rickettsial antibodies. Serological evidence of a fourfold increase in IgG-specific antibody titer reactive with spotted fever group rickettsial antigen by indirect immunofluorescence antibody assays between paired serum specimens was considered a confirmatory diagnosis for the rickettsial disease. RESULTS: Most of the patients were males 61.6%, and most 46.2% were in the age group of 20 -39 years. Most of the patients, 80.8% belonged to rural areas, and 48% belonged to the upper middle (II) class of the socio-economic class according to modified Kuppuswamy scale. Of the studied participants, a majority, 47.0%, were determined undiagnosed, while 15.4% studied participants were diagnosed to have a rickettsial disease. In patients positive for typhus group, 67.8% were IgM positive, 28.5% were IgG positive, and only 3% were positive for IgM and IgG. In patients positive for Scrub Typhus Group, 32.7% were positive for IgM, and 62.0% were positive for IgG, and only 5.0% were positive for both IgM and IgG. In patients positive for spotted fever group, 36.1% were positive for IgM, and 58.5% were positive for IgG, and only 5.5% were positive for both IgM and IgG. The prevalence of rickettsial disease was found to be 11.3%. CONCLUSION: Rickettsial diseases, typhoid and brucellosis, were the most prevalent diseased diagnosed among patients reporting to hospitals with undifferentiated febrile illness. Clinicians must consider rickettsial diseases as one of the differential diagnosis while treating patients with fever.

Role of genetic variants of Vitamin D receptor, Toll-like receptor 2 and Toll-like receptor 4 in extrapulmonary tuberculosis.

BACKGROUND: Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (MTB). Vitamin D deficiency and vitamin D receptor (VDR) gene abnormalities confer susceptibility to tuberculosis. Toll-like receptors (TLRs), such as TLR-2, are also important mediators of inflammatory response against Mycobacterium tuberculosis. We evaluated VDR, TLR-2 and TLR-4 gene polymorphisms in patients with extrapulmonary tuberculosis (EPTB). OBJECTIVES: To find out a possible association of Vitamin D receptor (VDR) (rs731236), TLR-2 (196-174 Ins > Del) and TLR-4 (Thr399Ile) gene polymorphisms with extrapulmonary tuberculosis in ethnic Kashmiri population. METHODS: A total of 100 extrapulmunary tuberculosis cases and 102 healthy controls were analyzed for Vitamin D receptor (VDR) (rs731236), TLR-2 (196-174 ins > del) and TLR-4 (Thr399Ile) gene polymorphisms using PCR-RFLP and Allele-Specific PCR methods. RESULTS: We found increased frequency of TLR-4 Thr/Ile heterozygous genotype in cases as compared with healthy controls (22% vs 5.8%). Thus acting as a risk factor for extrapulmonary tuberculosis, as was elucidated from statistical analysis [OR, 4.5; 95% CI (1.74-11.68); P < 0.001]. In case of TLR-2 (196-174 ins > del) we observed significant differences in the homozygous variant (Del/Del) genotype of cases and controls (28% in cases & 2.94% in controls). Thus, TLR-2 (Del/Del) genotype acts as a strong risk factor for extrapulmonary tuberculosis predisposition [OR, 12.2; 95% CI (3.5-42.69); P < 0.001]. We did not find any significant differences in the genotypic distribution of (VDR) (rs731236) T > C SNP between cases and controls (P > 0.05). CONCLUSION: TLR-4 (Thr/Ile) and TLR-2 (Del/Del) act as significant risk factors for extrapulmonary tuberculosis predisposition in ethnic Kashmiri population.

Bowel sounds in the chest: An uncommon presentation of adult hernia.

We report a case of a 65-year-old male, who presented with respiratory complaints of cough and breathlessness, managed initially as respiratory tract infection. However, the patient did not improve, and a thorough examination and imaging revealed herniation of a gut segment into the thorax. The patient was operated and respiratory symptoms improved dramatically.

Utility of GeneXpert in the diagnosis, reliance on urine microscopy and clinical characteristics of genitourinary tuberculosis at a tertiary care hospital.

BACKGROUND: One-third of the world's population is infected with tuberculosis (TB) with new infection occurring every second. In humans, TB is primarily caused by Mycobacterium tuberculosis(MTB). Genitourinary TB (GUTB) is still a major health problem in many developing countries including India and had been declared by the World Health Organisation as 'public health emergency' in 1993. MATERIALS AND METHODS: This is a prospective study conducted at a tertiary care hospital involving 46 patients who presented with clinical feature suggestive of GUTB - urine specimens of these 46 patients were analysed for acid-fast bacilli (AFB), AFB culture, GeneXpert, and other relevant investigations were done to reach the diagnosis. Majority of patients were female (65.25%). This is especially relevant to rural and low socioeconomic areas in developing countries where women's health is worse than men's (in terms of nutrition); women's risk of disease may be increased. Most of our patients were above 30 years of age and exhibited nonspecific symptoms such as dysuria, haematuria and frequency. All patients were put on antitubercular drugs and followed as per the guidelines. CONCLUSION: The sample size in the present study is small to arrive at a brisk inference, but it may safely be postulated that yield of detection for GeneXpert may be improved using multiple sampling, especially the early morning ones. It is also pertinent to mention here that GeneXpert may not be able to pick up mutant genomes.

Clinical profile of classical Fever of unknown origin (FUO).

BACKGROUND: The etiology of fever of unknown origin (FUO) may differ from different countries. This study was conducted to evaluate the etiology of FUO in patients attending SKIMS, a tertiary care teaching hospital, at Srinagar, Kashmir, India. METHODS: From July 2010 to September 2012, this study was done to examine the profile of patients with FUO. The classic FUO was defined as three outpatient visits or three days in the hospital without elucidation of cause of fever. Infectious agents, collagen vascular diseases and hematological malignancies as well as other etiologies were investigated when appropriate. The data were collected and analyzed. RESULTS: A total of 91 cases (62 males and 29 females), with age ranging from 16 to 80 years were investigated. The mean duration of fever before hospitalization was 26±4 days. The etiology of FUO was delineated in (66%) of cases, whereas, (25%) remained undiagnosed. Most common group of FUO was that of infectious diseases (44%) followed by collagen vascular diseases and malignancies (12 % each). Amongst the infection group, brucellosis and salmonellosis comprised the majority of cases (25% each). CONCLUSION: Infections are the most common cause of FUO followed by collagen vascular diseases in our region.

High altitude pulmonary edema among "Amarnath Yatris".

BACKGROUND: Annual pilgrimage (Yatra) to the cave shrine of Shri Amarnath Ji' is a holy ritual among the Hindu devotees of Lord Shiva. Located in the Himalayan Mountain Range (altitude 13,000 ft) in south Kashmir, the shrine is visited by thousands of devotees and altitude sickness is reportedly common. MATERIALS AND METHODS: More than 600,000 pilgrims visited the cave shrine in 2011 and 2012 with 239 recorded deaths. Thirty one patients with suspected altitude sickness were referred from medical centers en-route the cave to Sher-i-Kashmir Institute of Medical Sciences, a tertiary-care center in capital Srinagar (5,000 ft). The clinical features and the response to treatment were recorded. RESULTS: Thirty-one patients (all lowlanders, 19 male; age 18-60 years, median 41) had presented with acute onset breathlessness of 1-4 days (median 1.9 d) starting within 12-24 h of a rapid ascent; accompanied by cough (68%), headache (8%), dizziness and nausea (65%). Sixteen patients had associated encephalopathy. Clinical features on admission included tachypnea (n = 31), tachycardia (n = 23), bilateral chest rales (n = 29), cyanosis (n = 22) and grade 2-4 encephalopathy. Hypoxemia was demonstrable in 24 cases and bilateral infiltrates on radiologic imaging in 29. Ten patients had evidence of high-altitude cerebral edema. All patients were managed with oxygen, steroids, nifedipine, sildenafil and other supportive measures including invasive ventilation (n = 3). Three patients died due to multiorgan dysfunction. CONCLUSIONS: Altitude sickness is common among Amaranath Yatris from the plains and appropriate educational strategies should be invoked for prevention and prompt treatment.

Fat embolism syndrome in long bone trauma following vehicular accidents: Experience from a tertiary care hospital in north India.

BACKGROUND: Fat embolism syndrome (FES) is a clinical problem arising mainly due to fractures particularly of long bones and pelvis. Not much literature is available about FES from the Indian subcontinent. MATERIALS AND METHODS: Thirty-five patients referred/admitted prospectively over a 3-year period for suspected FES to a north Indian tertiary care center and satisfying the clinical criteria proposed by Gurd and Wilson, and Schonfeld were included in the study. Clinical features, risk factors, complications, response to treatment and any sequelae were recorded. RESULTS: The patients (all male) presented with acute onset breathlessness, 36-120 hours following major bone trauma due to vehicular accidents. Associated features included features of cerebral dysfunction (n = 24, 69%), petechial rash (14%), tachycardia (94%) and fever (46%). Hypoxemia was demonstrable in 80% cases, thrombocytopenia in 91%, anemia in 94% and hypoalbuminemia in 59%. Bilateral alveolar infiltrates were seen on chest radiography in 28 patients and there was evidence of bilateral ground glass appearance in 5 patients on CT. Eleven patients required ventilatory assistance whereas others were treated with supportive management. Three patients expired due to associated sepsis and respiratory failure, whereas others recovered with a mean hospital stay of 9 days. No long term sequelae were observed. CONCLUSION: FES remains a clinical challenge and is a diagnosis of exclusion based only on clinical grounds because of the absence of any specific laboratory test. A high index of suspicion is required for diagnosis and initiating supportive management in patients with traumatic fractures, especially in those having undergone an invasive orthopedic procedure.